Modulation of In Vivo T Cell Activation by an Acetylcholine-Esterase Inhibitor in Patients Chronically Infected with HIV

S46 exon 5 (P173W) and a deletion of 17 bp in exon 9. Analysis of parents and relatives showed the deletion to be of paternal origin and the substitution of maternal origin, but present also in a maternal uncle. Conclusion. A novel heterozygous mutation in IL12RB1 causes susceptibility to BCG infection after vaccination. In suspected cases, mutational screening should be performed even with normal expression of the IL12Rb1 receptor. doi:10.1016/j.clim.2007.03.305

F.93 Modulation of In Vivo T Cell Activation by an Acetylcholine-Esterase Inhibitor in Patients Chronically Infected with HIV Carlos Cantu-Brito, Investigator, Department of Neurology, Instituto Nacional de Ciencias Medicas y Nutricion SZ, Mexico City, Mexico, Sergio Ivan Valdes-Ferrer, Resident, Department of Neurology, Instituto Nacional de Ciencias Medicas y Nutricion SZ, Mexico City, Mexico, Jose Crispin, PhD Student, Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Medicas y Nutricion SZ, Mexico City, Mexico, Francisco Belaunzaran, Resident, Department of Infectious Diseases, Instituto Nacional de Ciencias Medicas y Nutricion SZ, Mexico City, Mexico, Maria Ines Vargas Rojas, PhD Student, Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Medicas y Nutricion SZ, Mexico City, Mexico, Juan Sierra, Investigator, Department of Infectious Diseases, Instituto Nacional de Ciencias Medicas y Nutricion SZ, Mexico City, Mexico, Jorge Alcocer Varela, Investigator, Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Medicas y Nutricion SZ, Mexico City, Mexico The immune system of patients with HIV is overstimulated. An increased fraction of in vivo activated CD4+ Tcells coupled with a decrease in regulatory Tcell numbers is a cardinal feature commonly observed. Vagal stimulation can modulate inflammatory response through T cell and macrophages by down-regulating their production of pro-inflammatory cytokines, namely TNF-α, IL-1, and IL-6. The aim of this work was to analyze if the administration of an acetylcholine-esterase (Ach-E) inhibitor is capable of diminishing immune over-stimulation in patients chronically infected with HIV. Methods: Nineteen HIV-infected patients with more than 250 CD4+ T cells, devoid of antiretroviral therapy, were assigned to pyridostigmine sulfate 90 mg/day or matching placebo. In every case, two peripheral blood samples were obtained: one before and one after 1 week of treatment. In vivo activated CD4+ T cells (HLA-DR+, CD69+) and regulatory T cells (CD4+CD25+Foxp3+) were quantified with flow cytometry. CD4+ T cell proliferation was quantified after stimulation with a polyclonal stimulus (either PHA or PMA + ionomycin). Results: Nine patients received pyridostigmine, 10 placebo. There were no basal differences between treatment and placebo groups. In vivo activated CD4+ T cells diminished significantly (p = 0.025) in patients who received pyridostigmine. Conversely, regulatory T cells increased in treated patients. Finally, CD4+ T cell proliferation was significantly lower in patients who received

Abstracts pyridostigmine (p = 0.026). Discussion: We found that the administration of a low dose of Ach-E inhibitors can successfully diminish CD4+ T cell over-stimulation in patients with chronic HIV infection.

doi:10.1016/j.clim.2007.03.306

F.94 CD4/CD8 T Cell Ratio Predicts HIV Infection in Infants: The NHLBI P2C2 HIV Study William Shearer, Professor, Baylor College of Medicine, Texas Children’s Hospital, Pediatrics, Houston, TX, Savita Pahwa, Professor, University of Miami, Miller School of Medicine, Miami, FL, Jennifer Read, Medical Officer, National Institute of Child Health and Human Development, Bethesda, MD, Sameera Wijayawardana, Biostatistician Student, Emory University Rollins School of Medicine, Atlanta, GA, Jing Chen, Assistant Professor, Emory University Rollins School of Medicine, Antanta, GA, Kirk Easley, Senior Associate, Emory University Rollins School of Medicine, Atlanta, GA, Paul Palumbo, Professor, Dartmouth Medical School, Hanover, NH, Elaine Abrams, Associate Professor, Columbia University, New York, NY, Steven Nesheim, Associate Professor, Emory University School of Medicine, Atlanta, GA Background: Although CD4 and CD8 T cell counts are available in many resource-poor settings, HIV DNA PCR tests are not. We analyzed data from the P2C2 HIV and CDC PACTS studies (overall HIV transmission rates: 17% and 18%, respectively) to evaluate the CD4/CD8 T cell ratio as a predictor of HIV infection among HIV-exposed infants. Methods: Data from the 3-month visit (45–150 days) for infants born to HIV-infected mothers enrolled in the P2C2 HIV study (79 HIV-infected, 409 uninfected) were analyzed. The CDC PACTS cohort (224 HIV-infected, 1015 uninfected) was used for validation. Results: The area under the ROC curve was higher for the CD4/CD8 ratio compared to the CD4 cell count (AUC = 0.83 and 0.75, P = 0.03). The mean CD4/CD8 ratio at the 3-month visit was 1.7 for HIV-infected infants and 3.0 for uninfected infants. A CD4/CD8 ratio of 2.4 was almost 2.5 times (95% CI for the likelihood ratio: 2.1–2.9) more likely to occur in an HIV-infected infant compared to an uninfected infant (test sensitivity 81%; posttest probability of HIV 33%). Model performance in the CDC PACTS validation sample was equally good (AUC = 0.78 for the CD4/CD8 ratio; good agreement between the predicted and observed risk of HIV). Conclusion: We conclude that the CD4/CD8 T cell ratio is a more sensitive predictor of HIV infection in infants than the CD4 T cell count and, when necessary, the CD4/CD8 T cell ratio may be used with caution to diagnose HIV infection. doi:10.1016/j.clim.2007.03.307

F.95 First Case of Human CD21 Deficiency— Association with Hypogammaglobulinemia Jens Thiel, MD, University Hospital Freiburg, Freiburg